Given their roles in DNA damage-related processes, we next investigated whether the presence of mutations in VHL, PBRM1, BAP1, SETD2, KDM5C, or TP53 correlated with the enrichment of any of the different DNA damage signatures by comparing enrichment scores between normal kidney and ccRCC with or without a mutation in each of the genes individually (Supplemental Figure 3). Here, SETD2 is linked to nonpapillary renal cell carcinoma.